The proposed research is a biophysical study of the process by which lipid membranes induce aggregation and pathologically mis-folded secondary structure in amyloid beta (Ab) proteins. It aims to define mechanistic links between two major themes in the pathogenesis of Alzheimer's disease: amyloid fibril formation and oxidative damage. It is hypothesized that these processes are linked through protein-lipid interactions, and we have developed novel instrumentation for characterizing these interactions. [unreadable] [unreadable] We are specifically proposing to (1) Determine the secondary structure of membrane-associated Af3 protein, (2) Correlate Ab folding and accumulation to membrane composition and source, and (3) Define potential consequences of Ab-induced oxidative membrane damage. [unreadable] [unreadable] This research addresses basic pathological mechanisms of Alzheimer's Disease by addressing the complex interrelationships between Ab fibril formation, lipid membranes, and oxidative damage in both synthetic membranes and membranes derived from pathologically afflicted human brain tissue. In this way, the concept of membrane-mediated amyloidogenesis will be developed on a molecular and pathologically-relevant level.